Bauquet Aurelie T, Jin Hulin, Paterson Alison M, Mitsdoerffer Meike, Ho I-Cheng, Sharpe Arlene H, Kuchroo Vijay K
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nat Immunol. 2009 Feb;10(2):167-75. doi: 10.1038/ni.1690. Epub 2008 Dec 21.
The inducible costimulatory molecule ICOS has been suggested to be important in the development of interleukin 17 (IL-17)-producing helper T cells (T(H)-17 cells) and of follicular helper T cells (T(FH) cells). Here we show that ICOS-deficient mice had no defect in T(H)-17 differentiation but had fewer T(H)-17 cells after IL-23 stimulation and fewer T(FH) cells. We also show that T(FH) cells produced IL-17 and that T(FH) cells in ICOS-deficient mice were defective in IL-17 production. Both T(H)-17 and T(FH) cells had higher expression of the transcription factor c-Maf. Genetic loss of c-Maf resulted in a defect in IL-21 production and fewer T(H)-17 and T(FH) cells. Thus our data suggest that ICOS-induced c-Maf regulates IL-21 production that in turn regulates the expansion of T(H)-17 and T(FH) cells.
诱导性共刺激分子ICOS被认为在产生白细胞介素17（IL-17）的辅助性T细胞（T(H)-17细胞）和滤泡辅助性T细胞（T(FH)细胞）的发育中起重要作用。在此我们表明，ICOS缺陷小鼠在T(H)-17分化方面没有缺陷，但在IL-23刺激后T(H)-17细胞较少，且T(FH)细胞也较少。我们还表明，T(FH)细胞产生IL-17，且ICOS缺陷小鼠中的T(FH)细胞在IL-17产生方面存在缺陷。T(H)-17细胞和T(FH)细胞均有更高水平的转录因子c-Maf表达。c-Maf的基因缺失导致IL-21产生缺陷以及T(H)-17细胞和T(FH)细胞减少。因此，我们的数据表明，ICOS诱导的c-Maf调节IL-21的产生，而IL-21又反过来调节T(H)-17细胞和T(FH)细胞的扩增。
